The development and maintenance of specific synaptic connections between retinal neurons is critical to its function. However, our understanding of neural circuit formation in the human retina remains limited. Within the last 10 years it has become possible to grow 3-dimensional, multi-layered retinal organoids derived from human stem cells. This advance permits the study of human retinal development and the establishment of synaptic connectivity. Our goal is to elucidate mechanisms underlying synapse formation and specificity in the first synapse of the human visual system. Access to patient-derived organoids allows us to understand this process in the disease state and following novel treatment paradigms such as gene therapy and cell-based therapy. We utilize a variety of techniques including live fluorescent imaging, electrophysiology, and gene editing in stem cell-derived human retinal organoids. The long-term goal of this work is to understand how synaptic connections are established and maintained in the human nervous system.

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